Pharmacology of Nitrates

Nitrates
Nitrates were the fi rst agents used to relieve angina. Th is group of drugs reduces myocardial ischemia, but may cause hypotension. Nitrates are still an important part of antianginal therapy.

Mechanism of Action
Nitrates primarily are eff ective in the venous circulation by relaxing vascular smooth muscle and reducing the left ventricle’s work. Th ese agents are administered to dilate the blood vessels and stop attacks of angina

Indications
Nitrates are used in the treatment of angina as coronary vasodilators. Nitrate preparations should be based on onset of action, duration of action, and patient compliance. Nitrate preparations are available in sublingual tablets, nitroglycerin spray bottles, topical nitroglycerin ointments, and transdermal patches. The sublingual route is the most common route of administration for nitroglycerin. This agent begins to work rapidly and lasts for about an hour. Th is is an ideal preparation for acute anginal pain.

Administration should begin as soon as the pain begins, and should not be delayed until the pain is severe. If one tablet is not sufficient, one or two additional tablets should be taken at fi ve-minute intervals. For persistent pain, the patient should see a physician, because he or she may have signs of a myocardial infarction. Th e shelf life of nitroglycerin is longer in a dark, tightly closed container. Aft er the container is opened, the drug is eff ective for approximately 30 days, and the date on which it was opened should be written on the container. Th irty days aft er the container is opened, the medication should be discarded and replaced with a new bottle.

Transdermal patches contain a reservoir of nitroglycerin. Th is agent is slowly released for absorption through the skin  The patches are slow in onset and are not eff ective for an ongoing anginal attack. The application site of the patch should be rotated daily to prevent irritation.

Topical ointment can also be used on the skin by using an applicator, and covering it with plastic wrap held in place with adhesive tape. The sites should be rotated to prevent local irritation.

Adverse Effects
Abrupt discontinuation of long-acting nitroglycerin preparations may cause angina. Vasodilation can lead to orthostatic hypotension, tachycardia, headache, dizziness, weakness, syncope, and blushing. Nitrate-induced headache is a result of the dilation of cerebral blood vessels. Nitrates may also increase intraocular and intracranial pressure. Continuous exposure to nitrates may lead to tolerance. Large doses of nitrate drugs can produce methemoglobinemia (the presence of methemoglobin in the blood).

Contraindications and Precautions
These agents are contraindicated in patients with hypersensitivity to nitrates, severe anemia, head trauma, and increased intracranial pressure. Nitrates are also contraindicated in glaucoma, hypotension, hyperthyroidism, and alcoholism.

Safety during pregnancy (category C) and lactation is not established. Nitrate drugs should also be used cautiously in severe liver or kidney disease.

Drug Interactions
A combination of nitrates and sildenafi l (Viagra) can cause prolonged and potentially life-threatening hypotension. Sildenafi l therapy should therefore be contraindicated in patients who use nitrates. Beta-blockers, calcium channel blockers, vasodilators, and alcohol can enhance the hypotensive effect of nitrates. IV nitroglycerin may antagonize the eff ects of heparin.